Italy has been the first-hit European country to face the outbreak of coronavirus disease 2019 (COVID-19). Aim of this survey was to assess in depth the impact of the outbreak on healthcare workers (HCW). A 40-item online survey was disseminated via social media inviting Italian HCW, with questions exploring demographics, health status and work environment of respondents. A total of 527 were invited to take part in March 2020, of whom 74% (n = 388) responded to the survey. Of these, 235 (61%) were women. HCW were mostly physicians (74%), from high-prevalence regions (52%). 25% experienced typical symptoms during the last 14 days prior to survey completion, with only 45% of them being tested for COVID-19. Among the tested population, 18 (18%) resulted positive for COVID-19, with 33% being asymptomatic. Only 22% of HCW considered personal protective equipment adequate for quality and quantity. Females and respondents working in high-risk sectors were more likely to rate psychological support as useful (OR, 1.78 [CI 95% 1.14–2.78] P = 0.012, and 2.02 [1.12–3.65] P = 0.020, respectively) and workload as increased (mean increase, 0.38 [0.06–0.69] P = 0.018; and 0.54 [0.16–0.92] P = 0.005, respectively). The insights from this survey may help authorities in countries where COVID-19 epidemic has not yet broken out. Management strategies should be promptly undertaken in order to enhance safety and optimise resource allocation.
4 November 2014 in Alimentary Pharmacology & Therapeutics
Summary: Background: A link between histone deacetylases (HDACs) and intestinal inflammation has been established. HDAC inhibitors that target gut‐selective inflammatory pathways represent a potential new therapeutic strategy in patients with refractory inflammatory bowel diseases (IBD).Aims: To review the use of selective HDAC inhibitors to treat gut inflammation and to highlight potential improvements in selectivity/sensitivity by additional targeting of HDAC‐regulating microRNAs (miRNAs).Methods: Original articles and reviews have been identified using PubMed search terms: ‘histone deacetylase’, ‘HDAC inhibitor’, ‘inflammatory bowel disease’, ‘gut inflammation,’ and ‘microRNA and HDAC’.Results: The use of butyrate in distal colitis provided the first evidence that inhibition of HDACs decreases intestinal inflammation in IBD. HDAC inhibitors, such as valproic acid, vorinostat and givinostat, reduce inflammation and tissue damage in experimental murine colitis. Potential mechanisms of action for HDAC inhibitors include increased apoptosis, reduction of pro‐inflammatory cytokine release, regulation of transcription factors and modulation of HDAC‐regulatory miRNAs. HDAC2, HDAC3, HDAC6, HDAC9 and HDAC10 isoforms seem to be specifically involved in chronic intestinal inflammation, justifying the use of selective inhibitors as new therapeutic strategies in IBD. Controlling miRNAs for these isoforms can be identified.Conclusions: The pro‐inflammatory influence of HDACs in the gut has been confirmed, but mostly in murine studies. Considerably more human data are required to permit development of selective HDAC inhibitors for IBD treatment. Inhibition of key HDAC isoforms in combination with modulation of HDAC‐regulatory miRNAs has potential as a novel therapeutic approach.
14 October 2016 in Expert Review of Clinical Immunology
Introduction: Anti TNF-α agents have become a significant advance in the management of ulcerative colitis, proving to induce, with rapid onset, clinical and endoscopic remission. However, there is still a considerable unmet medical need in ulcerative colitis. Areas covered: The aim of this review was to summarize the patterns of use and the effectiveness of anti TNF-α in ulcerative colitis, highlighting their current position in treatment algorithms. Moreover, we set out a five-year view hypothesizing different treatment strategies. Expert commentary: The rapid onset of action and the effectiveness in inducing mucosal healing are the most important pros of anti TNF-α, supporting present and future use. Conversely, the relevant risk of loss of response and the safety profile have raised several concerns. In the future, the advent of different molecular targeting therapies can improve the management of UC patients, evolving to individually tailored strategies.
31 July 2015 in Alimentary Pharmacology & Therapeutics
Background Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti‐TNF alpha. Patients with severe skin lesions unresponsive to topical therapy need to withdraw from treatment. Aim To estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti‐TNF alpha and to analyse its clinical correlates. Methods A retrospective cohort study on all IBD patients who started anti‐TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time‐dependent predictors were updated at each available time point. Results Four hundred and two patients were included. Participants contributed a total of 839 person‐years of follow‐up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person‐years. Cox‐regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36–4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12–0.92; P = 0.03). Conclusions Paradoxical psoriasis is a relevant side effect of anti‐TNF alpha therapy, with an incidence rate of five per 100 person‐years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti‐TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.
1 January 2015 in World Journal of Gastroenterology
Perianal disease is one of the most disabling manifestations of Crohn’s disease. A multidisciplinary approach of gastroenterologist, colorectal surgeon and radiologist is necessary for its management. A correct diagnosis, based on endoscopy, magnetic resonance imaging, endoanal ultrasound and examination under anesthesia, is crucial for perianal fistula treatment. Available medical and surgical therapies are discussed in this review, including new local treatment modalities that are under investigation.
Patients with Crohn's disease (CD) often require surgery over their clinical course. However, endoscopic and clinical recurrence of disease appear respectively in up to 80% and 30% of patients after one year. Thus, a prophylactic treatment is needed to reduce the possibility of recurrence. Both azathioprine and infliximab have been demonstrated to be effective, but head to head studies have not been performed so far. Aim of this open-label prospective study was to analyse endoscopic, histological and clinical recurrence after one year of treatment with azathioprine or infliximab as postoperative therapies in CD patients with "high risk" of recurrence. Consecutive CD patients who underwent curative ileocolonic resection were randomized (1:1) to receive infliximab (standard induction and maintenance schedule) or azathioprine (2.5 mg/kg/day) for 1 year. Co-primary endpoints were endoscopic, histological and clinical recurrence after 12 months of therapy. Twenty-two consecutive CD patients (15 male; median age 32 years, IQR 22-38) were enrolled after curative ileocolonic resection. Eleven patients were treated with infliximab and 11 received azathioprine. Among patients treated with azathioprine, 4/10 (40%) had endoscopic recurrence compared to 1/11 (9%) in the infliximab group (p=0.14). Eight out of 10 (80%) among those who received azathioprine had severe histological activity, whereas 2/11 (18%) in the infliximab group presented histological recurrence (p=0.008). No significant clinical differences were found between the two groups. Infliximab was more effective than azathioprine in reducing histological, but not endoscopic and clinical recurrence after curative ileocolonic resection in "high risk" CD patients.